It has been found that certain pharmaceuticals are absorbed to a degree through the skin. This is referred to as transdermal pharmaceutical absorption. One means of effecting transdermal absorption has been to distribute the pharmaceutical within a polymeric disc or a container of a gel, which is brought into contact with an area of the skin of the subject to be treated with the pharmaceutical. Also, ointments or lotions containing a desired pharmaceutical have been applied to an area of the skin of the subject to be treated. Problems encountered in such treatment include inadequate control over the rate and duration of transdermal absorption or the rate can be too slow in the case of certain dosage forms, especially from pharmaceutical-containing discs or pharmaceutical-containing gel container dosage units or pads. It has been found that the transdermal absorption rates of certain pharmaceuticals can be increased by use of absorption promoting compounds (also referred to as skin permeation enhancers) with the pharmaceutical to be absorbed when compounding the polymeric disc or the pharmaceutical-containing gel.
It is desired to improve the dosage unit forms or devices by which pharmaceuticals are transdermally absorbed, especially in view of the importance of administration of pharmaceuticals by this means. Desired transdermal absorption of pharmaceuticals would provide an avoidance of gastrointestinal incompatibility with the pharmaceuticals and unwanted destruction of the pharmaceutical by metabolism in the gastrointestinal tract and by a "first pass" hepatic metabolism. The transdermal absorption minimizes inter- and intra-patient variations regarding such incompatibilities and metabolisms. By transdermal absorption, it is deemed possible to provide more constant pharmaceutical concentration in the body and to realize a greater pharmaceutical efficiency. It is possible, by proper transdermal absorption, to reduce the frequency of effective dosing. Transdermal administration provides most of the advantages of intravenous dosing without the necessity of hospitalization and the accompanying discomfort and inconvenience.
With regard to specific pharmaceuticals to which this invention is directed, the morphinan narcotic analgesic hydromorphone is an illustration of a morphinan narcotic analgesic or antagonist pharmaceutical in which great loss of orally administered pharmaceutical occurs by first-pass through the liver. Therefore, oral administration of hydromorphone is a deficient means of administering hydromorphone as well as other morphinan narcotic analgesics and antagonists. Hydromorphone and other of the morphinan narcotic analgesics and antagonists can also be administered parenterally, but this method has the disadvantages of the discomfort and unpleasantness of injection as well as the hazards of injection. Hydromorphone and other of the morphinan narcotic analgesics and antagonists can be administered nasally according to U.S. Pat. No. 4,464,378.
There is clearly a need for improvements in means and methods for morphinan narcotic analgesic and antagonist therapy. Such a need could be provided by effective transdermal dosage unit forms and therapy processes, especially in view of the ease and convenience of administration and cessation of therapy.